This application requests funding to permit the purchase of an LC-MS-MS instrument that would provide a significant upgrade of the shared mass spectrometry capabilities available to researchers at the University of Iowa. The proposed instrument will be located in the University of Iowa High Resolution Mass Spectrometry Facility (UIHRMSF), and will be operated and maintained by a Ph.D.-level mass spectrometry specialist. The requested system consists of a quadrupole ion trap mass spectrometer capable of performing tandem mass spectrometry (MS-MS) experiments, and will be interfaced with a liquid chromatograph (LC). Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) will be available as ionization methods. Samples can be introduced either by LC or by direct infusion using a dual syringe pump. Currently, there are 44 research groups on campus that utilize the UIHRMSF, and nearly three-quarters of these are involved in biomedical research. MS-MS capability is not available on campus, and none of the major user groups listed in this application have access to LC-MS service. The proposed instrument will be configured for use as an open access system for the major users. Projects from seven NIH-supported major users groups are described in this proposal, although other biomedical researchers on campus will also have access to the instrument. These projects include: structure determination of natural products from fungi, characterization of novel nucleoside phosphonates, analysis of enzyme modifications, sequence analysis of neutral and sulfated oligosaccharides, structure determination of modified hemes, analysis of 18O-incorporation in ubiquitin, identification of oxygenated lipid metabolites, investigation of the structure of a proteinaceous anti-tumor agent and identification of 2H/1H exchange sites in proteins. Access to the state-of-the-art mass spectrometry capabilities provided by the proposed instrument would be beneficial to all of these research programs.